Re-programming by a six-factor-secretome in the patient tumor ecosystem during nutrient stress and drug response

• Published in: iScience 2024-10, Vol.27 (10), p.110932, Article 110932
• Main Authors: Elghetany, M. Tarek, Pan, Jie-Ling, Sekar, Karthik, Major, Angela, MF Su, Jack, Adesina, Adekunle, Hui, Kam-Man, Li, Xiao-Nan, Teo, Wan-Yee
• Format: Article
• Language: English
• Subjects: Cancer; Cell biology
• ISSN: 2589-0042; 2589-0042
• DOI: 10.1016/j.isci.2024.110932

Cancer cells need nutrients to grow and proliferate. During nutrient stress in the microenvironment, it is unclear if or how cancer cells can adopt alternative resources to re-wire and survive in patients. We discovered a 6-factor-secretome remarkably sustains a critical cell mass during nutrient stress in a pediatric embryonal brain tumor, atypical teratoid rhabdoid tumor (ATRT). Specific ATRT subtypes emerged as secretome-enriched, matching macrophage-enrichment patterns and were high-relapse-risk subtypes. The secretome alters drug response, protects against cell death, and provides pro-survival niches to rescue drugged cells. Secretome-grown tumor cells rearrange into a web-like architecture—stable during drug exposure, suggesting a mechanism for therapy resistance. Secretome prevents tumor cell death in aggressive tumor models, and in cerebrospinal dissemination, suggesting a role in tumor resistance/relapse. Our results unravel, a previously unexplored role of a specific 6-factor-secretome, providing an alternative fuel to sustain cancer cells during nutrient stress, and implications in relapse subtypes. [Display omitted] •Cancer cells use secretome as fuel to re-wire and survive during nutrient stress•Secretome alters drug response and protects tumor against cell death•Secretome-grown tumor cells rearrange into web-like architecture and resist the drug•Specific ATRT subtypes are secretome-enriched and are high-relapse-risk subtypes Cell biology; Cancer